Identification of Lysine Succinylome and Acetylome in the Vancomycin-Intermediate Staphylococcus aureus XN108

Abstract

Lysine succinylation (Ksucc) and acetylation (Kac) are two important protein posttranslational modifications (PTMs) that regulate numerous biological functions in prokaryotes and eukaryotes. However, the functions of Ksucc and Kac in Staphylococcus aureus are seldom described.

Biochemical and Cellular Characterization of the Function of Fluorophosphonate-Binding Hydrolase H (FphH) in Staphylococcus aureus Support a Role in Bacterial Stress Response

“…In E. coli , it has been shown that the stability of Ribonuclease R can be modified by acetylation . A recent proteomic study has revealed that Ribonuclease R (VacB/RNase II family exoribonuclease, AID39289.1), SmpB (SSrA-binding protein AID39290.1) as well as FphH (carboxylesterase, AID39288.1) have multiple acetylation sites in S. aureus , where SmpB also features one succinylation site . Thus, the hydrolytic removal of these post-translational modifications on Ribonuclease R and SmpB is a hypothetical function for FphH/YvaK that might link this esterase to the other members in the gene cluster.…”

The (patho)physiological roles of the individual deacylase activities of a sirtuin

“…CobB is the sirtuin protein present in bacteria. In certain bacterial species like Escherichia coli and vancomycin‐intermediate Staphylococcus aureus , a CobB protein has two enzymatic activities, that is, the deacetylase and desuccinylase activities (Colak et al., 2013; Tan et al., 2022); however, in other bacterial species like Streptomyces coelicolor , its CobB1 isoform (i.e., ScCobB1) is a dedicated deacetylase and its CobB2 isoform (i.e., ScCobB2) is a dedicated desuccinylase (Mikulik et al., 2012; Zhang, Li, et al., 2019). Therefore, ScCobB1 and ScCobB2 could be regarded as the deacylase‐specific mutants of the bifunctional CobB in certain other bacterial species and could be employed to study the (patho)physiological roles of the individual deacetylase and desuccinylase activities of a bifunctional CobB.…”

“…One major discovery in the sirtuin field has been that many sirtuins each possesses multiple deacylase activities acting on N ε ‐acyl‐lysine substrates with different acyl groups (Figure 1) (Abmayr & Workman, 2019; Anderson et al., 2017; Bheda et al., 2016; Chen et al., 2015; Chio et al., 2023; Colak et al., 2013; Delaney et al., 2021; Dong et al., 2022; Fan et al., 2023; Feldman et al., 2013; Gil et al., 2013; Huang, Zhang, et al., 2018; Ji et al., 2021; Jin et al., 2016, 2023; Li & Zheng, 2018; Liu et al., 2020; Mikulik et al., 2012; Olesen et al., 2018; Rajabi et al., 2018; Ringel et al., 2014; Seidel et al., 2016; Sun et al., 2022; Tan et al., 2022; Teng et al., 2015; Wang et al., 2023; Zhang et al., 2023; Zhang, Cao, et al., 2019; Zhang, Li, et al., 2019; Zhu et al., 2012; Zu et al., 2022). Specifically, SIRT1/2/3 are all able to catalyze efficiently the deacetylation and defatty‐acylation (e.g., demyristoylation) reactions; CobB from certain bacterial strains is able to catalyze the deacetylation and desuccinylation reactions with comparable catalytic efficiency; CobB from Escherichia coli was further found to catalyze the delactylation reaction with comparable catalytic efficiency to its deacetylase activity; SIRT1 is also able to catalyze deformylation reaction albeit being ~6.6‐fold less proficient than its deacetylase activity; SIRT1 was further found to be an in vivo debenzoylase and delactylase; SIRT2 is also able to catalyze debenzoylation, demethacrylation, and de‐4‐oxononanoylation (de‐4‐ONylation) reactions with more or less comparable catalytic proficiency to that of deacetylation; SIRT2 and SIRT3 were also found to possess an in vivo delactylase activity; SIRT3 is also capable of catalyzing proficiently the decrotonylation and de‐β‐hydroxybutyrylation reactions; SIRT4 is able to catalyze proficiently the deglutarylation and de‐3‐methyl‐glutarylation reactions; SIRT5 is able to catalyze proficiently the demalonylation, desuccinylation, and deglutarylation reactions; SIRT6 was found to catalyze both deacetylation and defattyl‐acylation (e.g., demyristoylation) reactions, with the former activity being weaker than the latter activity on isolated protein substrates; however, the former activity can be enhanced when the substrates are core histone proteins present in a nucleosome unit together with double‐stranded DNA (dsDNA), which has been rationalized very recen...…”

Recent Contributions of Proteomics to Our Understanding of Reversible Nε-Lysine Acylation in Bacteria

“…As mentioned here, there is growing evidence that there might be crosstalk among PTMs in bacteria. 63,77,79,80,83,125 As of now, this is largely based on the observation that a single lysine residue can be modified by multiple PTMs. Top-down MS would allow for the examination of all combinations of PTMs and different proteoforms that exist in the cell, under different growth conditions, or in the presence of environmental stresses.…”

“…Interestingly, 75% of succinylated sites were found to be acetylated, which agrees with the study on S. coelicolor (Figure ). The dually modified proteins were mainly involved in translation, aminoacyl-tRNA synthesis, and the glycolysis/gluconeogenesis pathways . Understanding the physiological significance of both modifications, identifying the mechanisms of acylation and deacylation, and deciphering the timing and chemical/biological cues regulating these modifications are of great interest.…”